The long-term objective of this work is to develop improved methods for identifying and characterizing large molecules, and to apply these methods to various biological problems. The methods include time-of-flight techniques for secondary ion mass spectrometry (SIMS), and the combination of liquid chromatography with time-of-flight mass spectrometry. Specifically it is proposed: 1. To make improvements in instrumentation and technique, including modifications to an existing time-of-flight spectrometer, construction of a new time-of-flight spectrometer of unusual design, and improvements to an existing liquid chromatograph. 2. To carry out studies on the basic physics of the secondary ion emission process, so as to obtain a better understanding of the process and to facilitate its application. 3. To apply time-of-flight mass spectrometry and its combination with liquid chromatography (LC/MS) to various samples of biological interest, in particular to fully protected nucleotides and natural mixtures of neuropeptides.